Prospective isolation and characterization of genetically and functionally distinct AML subclones

Bauke de Boer; Janine Prick; Maurien G Pruis; Peter Keane; Maria Rosaria Imperato; Jennifer Jaques; Annet Z Brouwers-Vos; Shanna M Hogeling; Carolien M Woolthuis; Marije T Nijk; Arjan Diepstra; Sebastian Wandinger; Matthias Versele; Ricardo M Attar; Peter N Cockerill; Gerwin Huls; Edo Vellenga; André B Mulder; Constanze Bonifer; Jan Jacob Schuringa

doi:10.1016/j.ccell.2018.08.014

Prospective isolation and characterization of genetically and functionally distinct AML subclones

Bauke de Boer, Janine Prick, Maurien G Pruis, Peter Keane, Maria Rosaria Imperato, Jennifer Jaques, Annet Z Brouwers-Vos, Shanna M Hogeling, Carolien M Woolthuis, Marije T Nijk, Arjan Diepstra, Sebastian Wandinger, Matthias Versele, Ricardo M Attar, Peter N Cockerill, Gerwin Huls, Edo Vellenga, André B Mulder, Constanze Bonifer, Jan Jacob Schuringa

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Abstract

Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.

Original language	English
Pages (from-to)	674-689.e8
Number of pages	24
Journal	Cancer Cell
Volume	34
Issue number	4
Early online date	20 Sept 2018
DOIs	https://doi.org/10.1016/j.ccell.2018.08.014
Publication status	Published - 8 Oct 2018

Keywords

acute myeloid leukemia (AML)
clonal heterogeneity
plasma membrane (PM)
proteome
genetically distinct subclones
DNase I hypersensitive site (DHS)
digital footprinting
FLT3-ITD
WT1
NRAS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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de_Boer_et_al_Prospective_Isolation_and_Characterization_of_Genetically_and_Functionally_Distinct_AML_Subclones_Cancer_Cells_2018
Contains public sector information licensed under the Open Government Licence v3.0. http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/
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de Boer, B., Prick, J., Pruis, M. G., Keane, P., Imperato, M. R., Jaques, J., Brouwers-Vos, A. Z., Hogeling, S. M., Woolthuis, C. M., Nijk, M. T., Diepstra, A., Wandinger, S., Versele, M., Attar, R. M., Cockerill, P. N., Huls, G., Vellenga, E., Mulder, A. B., Bonifer, C., & Schuringa, J. J. (2018). Prospective isolation and characterization of genetically and functionally distinct AML subclones. Cancer Cell, 34(4), 674-689.e8. https://doi.org/10.1016/j.ccell.2018.08.014

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title = "Prospective isolation and characterization of genetically and functionally distinct AML subclones",

abstract = "Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.",

keywords = "acute myeloid leukemia (AML), clonal heterogeneity, plasma membrane (PM), proteome, genetically distinct subclones, DNase I hypersensitive site (DHS), digital footprinting, FLT3-ITD, WT1, NRAS",

author = "{de Boer}, Bauke and Janine Prick and Pruis, {Maurien G} and Peter Keane and Imperato, {Maria Rosaria} and Jennifer Jaques and Brouwers-Vos, {Annet Z} and Hogeling, {Shanna M} and Woolthuis, {Carolien M} and Nijk, {Marije T} and Arjan Diepstra and Sebastian Wandinger and Matthias Versele and Attar, {Ricardo M} and Cockerill, {Peter N} and Gerwin Huls and Edo Vellenga and Mulder, {Andr{\'e} B} and Constanze Bonifer and Schuringa, {Jan Jacob}",

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de Boer, B, Prick, J, Pruis, MG, Keane, P, Imperato, MR, Jaques, J, Brouwers-Vos, AZ, Hogeling, SM, Woolthuis, CM, Nijk, MT, Diepstra, A, Wandinger, S, Versele, M, Attar, RM, Cockerill, PN, Huls, G, Vellenga, E, Mulder, AB, Bonifer, C & Schuringa, JJ 2018, 'Prospective isolation and characterization of genetically and functionally distinct AML subclones', Cancer Cell, vol. 34, no. 4, pp. 674-689.e8. https://doi.org/10.1016/j.ccell.2018.08.014

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T1 - Prospective isolation and characterization of genetically and functionally distinct AML subclones

AU - de Boer, Bauke

AU - Prick, Janine

AU - Pruis, Maurien G

AU - Keane, Peter

AU - Imperato, Maria Rosaria

AU - Jaques, Jennifer

AU - Brouwers-Vos, Annet Z

AU - Hogeling, Shanna M

AU - Woolthuis, Carolien M

AU - Nijk, Marije T

AU - Diepstra, Arjan

AU - Wandinger, Sebastian

AU - Versele, Matthias

AU - Attar, Ricardo M

AU - Cockerill, Peter N

AU - Huls, Gerwin

AU - Vellenga, Edo

AU - Mulder, André B

AU - Bonifer, Constanze

AU - Schuringa, Jan Jacob

PY - 2018/10/8

Y1 - 2018/10/8

N2 - Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.

AB - Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.

KW - acute myeloid leukemia (AML)

KW - clonal heterogeneity

KW - plasma membrane (PM)

KW - proteome

KW - genetically distinct subclones

KW - DNase I hypersensitive site (DHS)

KW - digital footprinting

KW - FLT3-ITD

KW - WT1

KW - NRAS

U2 - 10.1016/j.ccell.2018.08.014

DO - 10.1016/j.ccell.2018.08.014

M3 - Article

C2 - 30245083

SN - 1535-6108

VL - 34

SP - 674-689.e8

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

Prospective isolation and characterization of genetically and functionally distinct AML subclones

Abstract

Keywords

UN SDGs

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Birmingham Environment for Academic Research (BEAR)

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